Method of gasifying or degasifying a liquid containing cells

ABSTRACT

A method of adding or removing a gas to or from a solution of the gas in a liquid involves transferring the gas between the liquid and another fluid through a membrane unit. The membrane unit includes a membrane which is (i) substantially impermeable to the solvent and having a permeability to oxygen of at least 100 barrers; (ii) formed from an amorphous copolymer of perfluoro-2,2-dimethyl-1,3-dioxole; and (iii) is maintained at a temperature below the glass transition temperature of the copolymer. The fluid can be another liquid or a gas. The novel method provides very high rates of gas transmission between liquids and permits gasifying liquids without resort to sparging bubbles through the liquid. The method thus can gasify liquid with superior efficiency and without excessive agitation due to bubbling. These features result in economy of gas consumption and reduced need for gas recovery equipment, and when used in connection with a toxic or organic gaseous component, reduced requirements for additional pollution control equipment. The membrane material is resistant to fouling by liquids, and especially, by bioreactor mass. Hence, the novel method can remain in service for long duration without substantially diminished performance. Utilities for the novel method include purifying drinking water through ozonolysis, oxygenating bioreactors and blood; oxidizing volatile organic compounds in water; adding gaseous reactants to liquid chemical reactions and supplying oxygen to and removing volatile pollutants from waste water.

This application is a division of U.S. patent application Ser. No.08/735,922 filed Oct. 24, 1996.

FIELD OF THE INVENTION

This invention relates to a method of transporting a gas to or from asolution of the gas in a liquid through a substantially liquidimpermeable and gas permeable polymer membrane.

BACKGROUND AND SUMMARY OF THE INVENTION

The ability to transport a gas to or from the dissolved state in aliquid has many uses. These include purifying drinking water throughozonolysis, oxygenating bioreactors and restoring oxygen to blood;oxidizing volatile organic compounds in water; adding gaseous reactantsto liquid chemical reactions and supplying oxygen and removing volatilepollutants from waste water to name a few.

Generally in conventional methods of gasifying a liquid, the gas isbubbled directly into the liquid. Devices such as perforated or frittedsparging tubes and nozzles may be used to reduce the size of thebubbles. Although bubble size reduction improves the rate of masstransfer by raising the gas-liquid interfacial area per unit volume,bubbling is highly inefficient for gasifying a liquid and has additionalshortcomings. Due to contact inefficiency, bubbling normally requiresadding more than the required stoichiometric amount of gas. Excess gasmust be discarded or recovered. Furthermore, the discarded gasfrequently may be an undesirable pollutant and before it can be emittedto the environment, the gas must be treated. At the very least,discarding excess gas adds material cost without adding value to theprimary product. Recovery of excess gas also complicates the productmanufacturing process which adds still more cost. Process complicationsintroduced by the recovery of excess gas can include stripping entrainedliquid or upstream contaminants from the exhaust gas and measuring theconcentration of such liquid and contaminants in the recovered gas.Liquid entrained in the excess gas can contain dissolved solids whichtend to precipitate in the gas recovery equipment. Removal of thesesolids further adds to the difficulty of recovering the excess gas.

Bubbling also can be incompatible with the process for which the liquidis being gasified. For example, in a bioreactor, the agitation caused bybubbling can interfere with growth of fragile cells or destroy thecells. Gas bubbles entrained in oxygenated blood can be dangerous to anindividual and normally should be eliminated completely.

Gas permeable polymer membranes might present an attractive technologyfor conducting mass transfer of gases. U.S. Pat. No. 5,051,114 to S.Nemser, issued Sep. 24, 1991, which is incorporated herein by reference,teaches the use of permeable polymer membranes for enriching orseparating a gaseous organic compound in a gas or a gas mixture.However, most gas permeable membranes are not suited to transporting gasto or from a liquid. If the membrane is perforated or porous, gas canpass through the membrane too quickly and bubble into the liquid withthe attendant disadvantages noted above. Also, the liquid can leakthrough the perforations or pores to contaminate the gas. Additionallythe liquid and/or solids which might be present can clog the pores toreduce gas transfer.

Most nonporous polymer permeable membranes present too great a barrierto gas transfer for practical gasifying or degasifying a liquid. Lowfree volume gas permeable membranes of nonporous polymers have whollyinadequate gas permeability. Other known high free volume, nonporouspolymer, gas permeable membranes are not acceptable for transporting gasto or from a liquid. Polytrimethylsilylpropyne ("PTMSP") is one of fewknown high free volume, nonporous polymers potentially suitable for gaspermeable membranes. When used to gasify liquids, PTMSP membranes yieldinitially substantial but rapidly and dramatically declining gas flux.Although there may be other explanations, it is understood that thisflow rate reduction is caused by liquid filling the free volume andthereby obstructing gas flow. Furthermore, certain corrosive gases, suchas chlorine and ozone, chemically attack PTMSP. Silicone rubber isanother nonporous, polymer with potential use in gas permeablemembranes. Unfortunately, silicone rubber cannot be fabricated easilyinto thin membranes or thin coatings on high surface area substrates.Consequently, silicone rubber membranes usually include a thick polymerlayer which constrains gas flow to relatively low rates.

It is very desirable to provide a nonporous, permeable polymer membranecapable of transporting gas to and from the dissolved state in a liquidat high flow rates. According to the present invention it has beendiscovered that nonporous gas permeable membranes formed from certaincopolymers of perfluoro-2,2-dimethyl-1,3-dioxole ("PDD") allow gastransfer into and out of a liquid at high rate. Furthermore, the highgas flux can be maintained for extended duration.

The present invention thus provides a method of transferring a gaseouscomponent between two fluids having different partial pressures of thegaseous component, and wherein at least one of the two fluids is aliquid, the method comprising:

contacting one of the two fluids with a first side of a two-sided,membrane unit, the membrane unit including a membrane (i) beingsubstantially impermeable to the liquid and having a permeability tooxygen of at least 100 barrers; (ii) formed from an amorphous copolymerof perfluoro-2,2-dimethyl-1,3-dioxole; and (iii) being at a temperaturebelow the glass transition temperature of the amorphous copolymer; and

simultaneously contacting the second side of the two-sided, membraneunit with the other of the two fluids.

In one aspect this invention further provides a method of oxygenatingblood having a low blood oxygen partial pressure, the method comprising:

contacting blood with a first side of a two-sided, membrane unit, themembrane unit including a membrane (i) being substantially impermeableto blood and having a permeability to oxygen of at least 100 barrers;(ii) formed from an amorphous copolymer ofperfluoro-2,2-dimethyl-1,3-dioxole; and (iii) being at a temperaturebelow the glass transition temperature of the copolymer; and

simultaneously contacting the second side of the two-sided, membraneunit with a gaseous mixture containing oxygen at a partial pressurehigher than the low blood oxygen partial pressure.

In another aspect pertaining specifically to a bioreactor, the presentinvention additionally provides a method of oxygenating a liquidreaction medium containing living cells and having a low oxygen partialpressure, the method comprising:

contacting the liquid reaction medium with a first side of a two-sided,membrane unit, the membrane unit including a membrane (i) beingsubstantially impermeable to the liquid reaction medium and having apermeability to oxygen of at least 100 barrers; (ii) formed from anamorphous copolymer of perfluoro-2,2-dimethyl-1,3-dioxole; and (iii)being at a temperature below the glass transition temperature of thecopolymer; and

simultaneously contacting the second side of the two-sided, membraneunit with a gaseous mixture containing oxygen at a partial pressurehigher than the low oxygen partial pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a section view of a membrane unit according to one embodimentof the present invention.

FIG. 2 is a section view of a membrane unit according to anotherembodiment of the present invention.

FIG. 3 is a schematic illustration of a flat membrane unit, permeatormodule for use with the present invention.

FIG. 4 is a plot of dissolved oxygen concentration in water versus timeof water oxygenated at various pressure conditions using a membrane unitof the present invention compared with a conventional membrane unit.

FIG. 5 is a plot of dissolved oxygen concentration in water versus timeduring oxygenation of a bioreactor for the process of the presentinvention compared with a conventional process.

FIG. 6 is a partial section view of a preferred permeator moduleaccording to the present invention.

DETAILED DESCRIPTION

In a broad sense, the present invention involves a method oftransporting a gaseous component through a substantially liquidimpermeable and gas permeable membrane between two fluids, at least oneof which is a liquid. With respect to the liquid, the term "gasify" isused herein to mean that the concentration of the gaseous componentincreases in the liquid. Conversely, the term "degasify" means that thegaseous component is transported out of the liquid to the other fluid.

The gaseous component generally is a low molecular weight chemicalsubstance which exists in the gaseous state, i.e., as a gas atatmospheric pressure and about 25° C. The gaseous component can be apure substance or a mixture. It can be any of a broad range of chemicalspecies. Representative gaseous components include elemental gases suchas helium, hydrogen, neon, nitrogen, chlorine, argon, oxygen, kryptonand xenon; hydrocarbons such as methane, ethylene, ethane, acetylene,propane, propylene, cyclopropane, butane and butylene; halocarbons orhalohydrocarbons such as dichlorodifluoromethane, methylene chloride,and methyl chloride; and miscellaneous industrial and environmentalgases such as nitrous oxide, carbon dioxide, ozone, hydrogen sulfide,ammonia, sulfur dioxide, carbon monoxide, phosgene and any mixture ofany of them. Oxygen is a preferred non-mixture gaseous component.Oxygen/ozone, oxygen/nitrogen, oxygen/nitrogen/ozone are preferredmixtures; and air and air/ozone are more preferred.

It is convenient to refer to the fluids on opposite sides of the gaspermeable membrane as the source fluid and destination fluid withrespect to the direction of migration of the gaseous component. At leastone of the two fluids is in the liquid state. That is, the fluid on atleast one side of the membrane is a liquid. The fluid on the other sidecan be a gas or a liquid. The source fluid, the destination fluid orboth can be liquid. An important feature of the novel method is that thegaseous component is not present in the gaseous state in the liquid insubstantial amount. Instead, the gaseous component can be dissolved inthe liquid or it can react quickly with the liquid or other substancesin the liquid. Consequently, the liquid can be considered to act as asolvent for the gaseous component. Provided that the gaseous componentis present in the liquid below saturation, the gaseouscomponent-containing fluid will remain liquid and no free gas willappear, i.e., bubbling will not occur.

The liquid can be a single compound or a mixture. A wide variety ofliquids such as aqueous and nonaqueous solvents can be used according tothe present invention. Liquids can include water; alcohols; ethers;ketones; esters; and combinations of these. Representative alcoholsinclude ethanol, butanol, and ethylene glycol. Representative ethersinclude dimethylether, diethylether and anisole. Representative ketonesinclude acetone, ethylmethylketone and diethylketone. Representativeesters include methylacetate, methylpropionate and ethyl acetate.Representative combinations include cellosolve; ethylcellosolve;acetylcarbinol; cellosolve acetate; polyethylene ether glycol,methoxyacetone; methylmethoxy acetate and methylketo butyrate. Water isa preferred liquid for use in the present invention.

The membrane is formed from an amorphous copolymer of a certainperfluorinated dioxole monomer, namelyperfluoro-2,2-dimethyl-1,3-dioxole ("PDD"). In some preferredembodiments, the copolymer is copolymerized PDD and at least one monomerselected from the group consisting of tetrafluoroethylene ("TFE"),perfluoromethyl vinyl ether, vinylidene fluoride andchlorotrifluoroethylene. In other preferred embodiments, the copolymeris a dipolymer of PDD and a complementary amount of TFE, especially sucha polymer containing 50-95 mole % of PDD. Examples of dipolymers aredescribed in further detail in U.S. Pat. Nos. 4,754,009 of E. N. Squire,which issued on Jun. 28, 1988; and 4,530,569 of E. N. Squire, whichissued on Jul. 23, 1985. Perfluorinated dioxole monomers are disclosedin U.S. Pat. No. 4,565,855 of B. C. Anderson, D. C. England and P. R.Resnick, which issued Jan. 21, 1986. The disclosures of all of theseU.S. patents are hereby incorporated herein by reference.

The amorphous copolymer can be characterized by its glass transitiontemperature ("T_(g) "). Glass transition temperature property of apolymer is understood in the art. It is the temperature at which thecopolymer changes from a brittle, vitreous or glassy state to a rubberyor plastic state. The glass transition temperature of the amorphouscopolymer will depend on the composition of the specific copolymer ofthe membrane, especially the amount of TFE or other comonomer that maybe present. Examples of T_(g) are shown in FIG. 1 of the aforementionedU.S. Pat. No. 4,754,009 of E. N. Squire as ranging from about 260° C.for dipolymers with 15% tetrafluoroethylene comonomer down to less than100° C. for the dipolymers containing at least 60 mole %tetrafluoroethylene. It can be readily appreciated thatperfluoro-2,2-dimethyl-1,3-dioxole copolymers according to thisinvention can be tailored to provide sufficiently high T_(g) that amembrane of such composition can withstand exposure to steamtemperatures. Hence, membranes of this invention can be made steamsterilizable and thereby suitable for various uses requiring sterilematerials, especially those involving biological materials. Preferably,the glass transition temperature of the amorphous copolymer should be atleast 115° C.

The PDD copolymer makes the gas permeable membrane of the novel methoduniquely and particularly well suited to accomplish the transport of agaseous component to or from a liquid. Firstly, the amorphous copolymeris both hydrophobic and organophobic. This property makes the membranematerial substantially impermeable to a wide variety of liquids.Impermeability to liquid importantly prevents liquid leakage between thefluids, a condition sometimes referred to as "break-through" or "wettingout" of the membrane. The term "substantially impermeable" means thatthe liquid fluid will not break through the membrane even when asignificant positive pressure differential is applied across themembrane. For example, a 50/50 isopropanol/water solution at up to about207 KPa (30 psig) pressure will not break through a membrane of PDDcopolymer into an atmospheric pressure, gas-filled chamber. Suchbreak-through ordinarily can be detected by visual inspection. Theextreme hydrophobicity and organophobicity of the PDD copolymer alsomakes the gas permeable membrane not more than negligibly soluble orswellable in a wide range of liquids. This characteristic assures thepreservation of the structural integrity and dimensional stability ofthe membrane while in contact with many liquid compositions.

Secondly, the amorphous copolymer can be applied readily in thin layerson high surface area per unit volume substrates, such as the insideand/or outside surfaces of hollow fibers. The amorphous copolymer usedin the present invention has very good permeability. For example,PDD/TFE copolymer membranes exhibit a permeability for oxygen of atleast 100 barrers, especially at least 200 barrers and in particular atleast 500 barrers. Certain conventional gas permeable membrane materialsmay have comparable permeabilities, however, they cannot easily beformed into thin layers on high surface area per unit volume substrates.Normally, these materials are formed into flat sheet membranes. Becausethe PDD copolymers can be thinly coated onto structures such as hollowfibers, the membranes can be packaged in modules which havesignificantly higher density of surface area available for mass transferthan an equivalent volume of conventional, flat sheet gas permeablemembranes. Consequently, the present method provides superior gas fluxinto or out of liquids than conventional methods due to the combinationof high gas permeability and the ability to assemble very compactmodules using high surface area substrates with thin coatings ofpermeable membrane.

Thirdly, PDD copolymer membranes additionally possess a selectivityamong gaseous components, most notably a selectivity of oxygen overnitrogen. Preferably the oxygen/nitrogen selectivity will be at leastabout 1.5:1. The gas selectivity of the PDD copolymer membranes can beexploited conveniently to test the membranes for coating defects. Theneed for PDD copolymer to completely coat the substrate is accentuatedin certain embodiments of the present invention which involve anextremely thin layer of amorphous copolymer coated on a high surfacearea per unit volume substrate. The detection of defects might otherwisebe difficult because the copolymer layer is so thin. However, themembrane can be evaluated easily for absence of holes, for example, byexposing one side of the membrane to a known, constant pressure, mixtureof selected gases and analyzing the atmosphere on the other side forconcentration of the gases consistent with the selectivity of themembrane composition.

Fourthly, the PDD copolymer membrane of this invention is very resistantto fouling by liquids. Accordingly, the membrane has the advantageousability to sustain for extensive duration high gas flux to or from aliquid with which the membrane is in contact. Furthermore, the high gasflow rate stability will be largely unaffected by the presence ofcontaminants in the fluids. Therefore, the liquid in contact with themembrane may exist in a wide range of purity. For example, the novelmethod can be used to transport a gaseous component to or from water ofany grade ranging from reagent quality, demineralized water to processquality water, such as brackish water, salt water, and environmentalwaste water containing various contaminants. Moreover, the excellent gasflux stability makes the present invention particularly useful forgasifying or degasifying biological fluids. Biological fluids includehuman and other animal natural body fluids such as blood, and othernatural, synthetic or combined liquid media for cell culturing. Suchfluids typically contain cells and other microorganisms which tend toadhere to and grow on many substrate materials. PDD copolymer membranesto a great extent can resist adhesion and maintain good gas flow inbiological fluid systems.

Preferred utilities for the present invention include ozonating sanitaryor industrial waste water to remove undesirable microorganisms andorganics; remediation by oxygenating natural streams, ponds andwaterways depleted of oxygen by industrial waste contamination or farmland run off; oxygenating water in tanks and ponds for purposes ofaquaculture; and depleting oxygen in reactors for anaerobic reactions orboiler water feed. The novel method is particularly preferred for use inbioreactor systems. The term "bioreactor" is used herein to meanreaction equipment for carrying out processes which incorporate livingorganisms, such as cells and bacteria, as the product of such processesor as agents for producing a chemical product. The oxygenation of bloodand the oxygenation of cell culture media to enhance cell growth areexamples of bioreactor system operations.

The gas permeable membrane can be a monolithic film. To maintainstructural integrity, such a film should be thick enough to withstandpressure differences between the fluids. However, to maximize the rateof gas transmission the membrane should be thin. Preferably the membraneof this invention includes a thin layer or coating of PDD copolymer. Thelayer or coating is placed on a porous substrate which providesstructural strength and minimal flow resistance. The composite ofamorphous copolymer and porous substrate thus forms a membrane unit. Theterm "membrane unit" is used occasionally herein to mean either a gaspermeable membrane or such membrane affixed coextensively over the gastransfer area with a substrate. Useful membrane units include, but arenot limited to, thin film composite films and composite hollow fibers.The structure of the substrate should be designed to have substantialporosity so as not to impede the flow of the gaseous component. Theporosity of the substrate can be effected by perforations or microscopicpores. Representative porous substrates include a rigid, perforatedsheet; a porous woven fabric; a monolithic microporous polymer film anda microporous, hollow fiber. To maximize gas flux, the thickness of thePDD copolymer membrane preferably should be less than about 10 μm, andmore preferably, less than about 1 μm.

A 1 μm thickness coating on the outside of a 250 μm outside diameterpolypropylene hollow fiber yields a mass transfer area per unit volumeof 8.2 cm² /cm³ with a fiber packing density of 20%. In contrast,silicone rubber cannot be easily coated on hollow fibers. The typicalarea density for a flat sheet geometry membrane structure is only 1.1cm² /cm³ or one eighth of packed hollow fibers. As shown in the examplesfollowing, below, the gas transmission rate per unit area throughmembrane structures based on copolymers ofperfluoro-2,2-dimethyl-3,1,-dioxole are approximately three to fourtimes that of conventional materials such as silicone rubber. Hence, themethods of the present invention provide about 25-30 times thevolumetric efficiency of gas transmission to liquid of conventionalmembranes (i.e., about 3.5 flux enhancement factor×8 area densityimprovement factor).

The nature of the membrane unit can be appreciated with reference toFIG. 1. The membrane unit 10 includes a layer of amorphous copolymermembrane 1 deposited on a porous substrate 3. The membrane unitcharacteristically has two sides 2 and 4, each in contact with adifferent one of the two fluids. Gaseous component in source fluid 6will migrate through the support structure to dissolve in destinationfluid 8. As previously mentioned, copolymers of PDD are very inert toliquids, i.e., the copolymer generally does not clog with non-gaseouscomponents of the fluid. In addition, mass transfer of gases isgenerally slower in both liquids and porous substrate material thanwithin a gas phase. Therefore, to achieve and maintain stability ofmaximum flux, the amorphous copolymer membrane 1 preferably shouldcontact one of the fluids 8 which is a liquid. It is acceptable toreverse position of fluids 6 and 8, i.e. so that membrane unit side 2contacts the gaseous fluid and side 4 contacts the liquid, however, gasflux could be reduced because of resistance to mass transfer ofdissolved gaseous component through the substrate.

FIG. 2 shows a membrane unit 20 well suited to liquid-to-liquid gastransfers, i.e., in which a gas is transferred between two liquids 16and 18. Such a membrane unit includes an optional, second coating 15 ofamorphous copolymer. The second coating can be affixed to the face 13 ofthe substrate material 17 nonadjacent to first coating 11. That is, themembrane unit is a sandwich configuration comprising a porous substrate17 between two amorphous copolymer membranes, 11 and 15. The amorphouscopolymers of the two coatings can be the same or different.

The membrane units of the present invention may be manufactured by avariety of methods known to those skilled in the art, including coatingtechniques such as dipping, spraying, painting and applying by doctorblade. PDD copolymers are amenable to solvent or melt processing, whileother fluoropolymers tend to be only melt processible. The solventprocessing capability permits PDD copolymers to be coated in very thinfilms on high surface area per unit volume substrates. Consequently, thepresent invention can effect high gas transfer rates that are difficultto match through membrane units produced by melt processing techniques.

Broadly described, the mass transfer through the membrane will be drivenby a difference between partial pressures of the gaseous component inthe two fluids. Generally, the gaseous component will migrate across theamorphous copolymer membrane from the source fluid in which it ispresent at high partial pressure to the destination fluid in which it isat lower partial pressure. For example, oxygen deficient water can beoxygenated by contacting one side of a membrane unit according to thisinvention with the water and contacting the second side with air.Raising the partial pressure of the gaseous component in the sourcefluid normally increases the driving force for migration through themembrane. Hence, in this example, the partial pressure of oxygen in thewater can be increased further, by changing the fluid on the second sideto mixtures of increased oxygen partial pressure ranging up tosubstantially pure oxygen. Alternatively, the dissolved oxygen partialpressure can be increased by raising the absolute pressure of the sourcefluid, or by combining increased oxygen partial pressure and raisedsource fluid absolute pressure.

The method of gas transfer through a gas permeable membrane according tothe present method provides great flexibility in choosing operatingconditions to optimize the rate of transfer to or from a liquid. Thatis, the unique combination of substantial liquid impermeability and highgas permeability of the PDD copolymer membrane permits operatingconditions for each of the two fluids to be set independently of theother. By way of example, it can be appreciated by one of ordinary skillin the art, that a liquid has greater capacity to retain a gaseouscomponent in the dissolved state at higher liquid pressure. Therefore, agreater amount of dissolved gaseous component can be introduced into aliquid without producing gas bubbles by raising liquid pressure. Becauseof the notably high resistance to liquid break-through of PDD copolymersmentioned earlier, a liquid in contact with a PDD copolymer membrane canbe successfully held at relatively high pressure to improve gassolubility. In the process of gasifying a destination liquid with asource gas on the opposite side of the membrane, the pressure of theliquid can exceed the pressure of the source gas without substantialrisk of leaking liquid into the source gas. For such a process, thedifference of liquid pressure over gas pressure can be at least 13.8 KPa(2 psi), preferably at least 34.5 KPa (5 psi), and more preferably, atleast 68.9 KPa (10 psi). The pressure of the source fluid and thedestination fluid each independently can be slightly below, about equalto, or above atmospheric pressure. As will be appreciated by personsskilled in the art, the migration of gaseous component through themembrane can be driven solely by a difference of partial pressures ofthe component in the source and destination fluids. Thus it is desirableto maintain the liquid at superatmospheric pressure to maximize gassolubility.

The novel method will usually be operated at about ambient temperature,but may be at higher temperatures. However, the membranes should be usedat a temperature below the glass transition temperature, and especiallyat least 30° C. below the glass transition temperature of the amorphouscopolymer used to the membrane. As previously explained, PDD copolymerscan have exceptionally high T_(g). Hence, the amorphous copolymermembranes used in the method of the present invention are capable ofbeing utilized at elevated temperatures, including in some embodimentsat temperatures above 100° C. Of course, the operating temperatureshould be maintained below the boiling point of the liquid to avoid gasbubbling. The method of the present invention may be operated atrelatively low temperatures, e.g., about 10° C.

The examples hereinafter show that the membranes according to thepresent invention are capable of gasifying and degasifying liquids atvery high flux of gaseous component. These examples further demonstratethe stability of mass transfer rate of these membranes in liquidgasifying service. That is, the high flux of gaseous component into andfrom a liquid can be sustained for extended duration. These featuresmake the novel methods for gasifying and degasifying liquids of greatpractical significance.

A preferred apparatus for implementation of the novel gasifying ordegasifying method is illustrated schematically in FIG. 6. The apparatusshown includes a generally cylindrical permeator module 60 equipped witha plurality of membrane units 62 disposed within a shell side cavity 64defined by the inside surface of wall 65 of the module, inlet tube sheet66 and outlet tube sheet 67. The term "permeator module" is used hereinto mean an apparatus which includes a plurality of membrane unitsgenerally within a common housing and which units are adapted, as in amanifolded configuration, to cooperatively function with a single firstfluid stream and a single second fluid stream. The spaces between endplates 68 and 69 and inlet and outlet tube sheets further define inletand outlet plenums 61 and 63, respectively. Each membrane unit is agenerally tubular structure including a hollow fiber substrate with athin coating of amorphous copolymer over the complete exterior surfaceof the fiber. Ends of the membrane units terminate at the inlet andoutlet tube sheets in the manner that the space within the hollow fibersis in fluid communication with the inlet and outlet plenums. The spaceinside the permeator module within the inlet and outlet plenums andinside the hollow fibers may be designated as the "tube side" of themodule. The membrane unit ends are sealed to the tube sheets so that thespace within the fibers is isolated from the shell side cavity 64. Thepermeator module is further equipped with first fluid inlet and outletports 71 and 72, respectively. First fluid inlet port 71 is mounted onend plate 68 and opens through the end plate in fluid communication withinlet plenum 61. First fluid outlet port 72 is mounted on end plate 69and opens through the end plate in fluid communication with outletplenum 63. Second fluid inlet port 73 and second fluid outlet port 74are mounted on the shell of the permeator module and open through thewall 65 in fluid communication with the shell side cavity 64. In theillustrated embodiment, second fluid inlet and outlet ports are shown atopposite ends of the permeator module. The shell side cavity canoptionally include one or more internal baffles 75, only one of which isshown in section view, which provide structural support for the membraneunits. The baffles will contain openings 76, only one of which is shown,adapted to create a continuous, maze-like path between second fluidinlet and outlet ports. The membrane units can be grouped in bundlescomprising multiple units and a permeator module can include a pluralityof bundles.

In use, a first fluid, for example a gas mixture including a permeatinggaseous component, can be caused to flow through the tube side. A sourceof the gas mixture is connected to first fluid inlet port and the gasmixture is permitted to enter inlet plenum 61, pass through the interiorof hollow fibers 62, discharge to outlet plenum 63 and exhaust throughfirst fluid outlet port 72 to a collection reservoir. Second fluid canbe introduced through second fluid inlet port 73 and pumped through theshell side cavity around the membrane units and through the baffleopenings to ultimately reach second fluid outlet port 74 for collection.In the illustrated embodiment in which the outside surfaces of thehollow fibers are coated with amorphous copolymer, preferably the tubeside (first) fluid will be a gas and the shell side (second) fluid willbe a liquid. It can be seen that the permeating gaseous component willmigrate through the coating of amorphous copolymer between first andsecond fluids.

It can readily be appreciated that many variations in the modes ofoperation, number, shape and placement of permeator module elements aresuitable for use in the present invention. Variations to the embodimentshown in FIG. 6 which are contemplated as falling within the breadth ofthe present invention include, for example, (a) coating the amorphouscopolymer coating on the interior surface of the hollow fiber or on bothinterior and exterior surfaces; and (b) conducting the liquid throughthe tube side and causing a gas or another liquid to flow through theshell side. As stated elsewhere herein, the liquid state fluidpreferably will be in contact with the amorphous copolymer side of themembrane unit. Accordingly, when the liquid flows through the tube side,preferably the inside of the hollow fibers will be coated with theamorphous copolymer. Conversely, as in the embodiment illustrated inFIG. 6, the coating will be on the outside surface of the fibers whenthe liquid is on the shell side of the permeator module.

In another contemplated embodiment, one or more fluid ports can becapped closed. For example the first fluid port can be shut. This"dead-heading of the tube side fluid, tends to cause the tube side fluidpressure to equilibrate with the pressure of the fluid source. In stillanother embodiment, the tube assembly, i.e., the fluid inlet port, inletplenum, tubes, outlet plenum and outlet port, can be adapted without theshell. The sub-unit can be immersed in fluid in a process or storagecontainer to gasify or degasify that fluid without the need to pump thefluid through a shell side of the module.

This invention is now illustrated by examples of certain representativeembodiments thereof, wherein all parts, proportions and percentages areby weight unless otherwise indicated. Unless otherwise stated or thecontrary is evident from context, all pressures referred to herein arerelative to atmospheric pressure.

EXAMPLES Examples 1-13

A dipolymer of 85 mole % perfluoro-2,2-dimethyl-1,3-dioxole and 15 mole% tetrafluoroethylene (hereinafter, "Polymer A") was coated onto thefollowing three types of hollow fiber supplied by Spectrum Microgon(Laguna Hills, Calif.):

"Substrate A": Cellulose ester hollow fiber of 800 μm outer diameter,600 μm inner diameter, and 0.10 μm pore size;

"Substrate B": Polysulfone hollow fiber of 660 μm outer diameter, 500 μminner diameter, and 50,000 molecular weight cut off ("MWCO") pore size;and

"Substrate C": Polypropylene hollow fiber of 240 μm outer diameter, 200μm inner diameter, and 0.05 μm pore size.

The hollow fibers were coated on either the inside or outside surfaceswith coatings of thicknesses stated in Table I. Coated fibers weremounted in a permeator module substantially as in FIG. 6 havingeffective surface areas as indicated in the table. The oxygen/nitrogenselectivity ratios of the coated fibers were measured in accordance withthe procedures described in U.S. Pat. No. 5,051,114. As can be seen fromTable I, all the selectivity ratios were sufficiently above 1.4 toconfirm that the coating was fully intact over substantially all of thehollow fiber substrate surfaces.

Measurement of thickness of Polymer A coating on the hollow fibersubstrates involved capping the first fluid outlet port and the secondfluid inlet port and measuring the permeation rate of a gas across themodular membrane units at known conditions. By comparing the permeationrates to those of flat sheets of Polymer A of known thickness of about25-50 μm, the average thicknesses of the coated fibers were calculated.

                  TABLE I    ______________________________________                  Coating  Area    Thickness                                          Selectivity    Support Material                  Location (cm.sup.2)                                   (μm)                                          0.sub.2 /N.sub.2    ______________________________________    Ex. 1 Cellulose Ester                      Outside  50    0.7    1.7    Ex. 2 Cellulose Ester                      Outside  50    0.9    1.7    Ex. 3 Cellulose Ester                      Outside  50    1.2    1.7    Ex. 4 Cellulose Ester                      Inside   50    1.5    1.7    Ex. 5 Polysulfone Outside  22    1.9    1.5    Ex. 6 Polysulfone Inside   680   0.2    1.7    Ex. 7 Polypropylene                      Outside  63    0.8    1.8    Ex. 8 Polypropylene                      Outside  250   0.9    1.7    Ex. 9 Polypropylene                      Outside  250   0.9    1.9    Ex. 10          Polypropylene                      Outside  850   0.6    1.7    Ex. 11          Polypropylene                      Inside   200   0.5    1.8    Ex. 12          Polypropylene                      Inside   1000  1.4    1.9    Ex. 13          Polypropylene                      Inside   1000  1.0    1.8    ______________________________________

These examples show that perfluoro-2,2-dimethyl-1,3-dioxole amorphouscopolymer can be coated as thin films on hollow fibers suitable forliquid gasification/degasification service.

Examples 14-16 and Comparative Examples 1-3

A clear shell permeator module substantially as shown in FIG. 6 wasprepared using certain polypropylene hollow fibers coated on the outsidewith a 2-6 μm layer of Polymer A. A solution of 50/50isopropanol("IPA")/water was pumped through the shell side of thepermeator module. The tube side was vented to ambient atmosphere.

The IPA solution pressure was raised until solution broke through themembrane unit as indicated by visual observation of liquid in the tubeside space. The oxygen/nitrogen selectivity of the permeator module wasdetermined according to the procedure cited in Examples 1-13. Thepressures of break-through onset of various samples having an assortmentof oxygen/nitrogen selectivities were determined and recorded as shownin Table II. The test also was performed on an uncoated polypropylenehollow fiber.

                  TABLE II    ______________________________________                          O.sub.2 /N.sub.2                                    Breakthrough Press.    Example Material      Selectivity                                    Kpa (psig)    ______________________________________    Ex. 14  Substrate C   2.0       >1240 (180)*    Ex. 15  Substrate D** 1.8       448 (65)    Ex. 16  Substrate C   1.7       413 (60)    Comp Ex 1            Substrate D   1.4       172 (25)    Comp Ex 2            Substrate D   1.2       172 (25)    Comp Ex 3            Uncoated Substrate D                          0.9       34.5 (5)    ______________________________________     *breakthrough exceeded 1.24 MPa (180 psig) limit of test equipment     **200 μm I.D./250 μm O.D. 0.05 μm pore size polypropylene hollow     fiber from Hoechst Celanese.

IPA solution used in these experiments is representative of low surfacetension fluids which are used in bioreactors. Comp. Ex. 3 demonstratesthat at low pressure, IPA solution breaks through the uncoatedsubstrate. In Comp. Exs. 1 and 2, the onset of break-through held off tothe higher pressure of 172 KPa (25 psig). Break-through in these sampleswas probably caused by incomplete coating of the substrate as evidencedby the low O₂ /N₂ selectivity ratio. In contrast, samples withselectivity ratios higher than 1.4 were able to withstand break throughuntil pressures significantly higher than 172 KPa (25 psig) had beenachieved. High selectivities of these samples indicated that the PDDcopolymer coating was fully continuous over the surface of thesubstrate. The high onset pressures of break-through of the operativeexamples reveal that pressure of a liquid containing dissolved gas in aPDD copolymer membrane unit can be raised considerably to significantlyincrease the solubility of the dissolved gas. In this way gas migrationinto the liquid without bubbling and rate of gasification can beenhanced.

Example 17 and Comparative Examples 4-5

The following three types of flat sheet membrane units were prepared:(Ex. 17) a composite membrane unit consisting of a layer of 1 μmthickness non-porous Polymer A on a 100 μm thickness Gore-Tex™ expandedpolytetrafluoroethylene (e-PTFE) porous layer; (Comp. Ex. 4) amonolithic uncoated 100 μm e-PTFE porous sheet; and (Comp. Ex. 5) a 1250μm thickness monolithic non-porous silicone rubber sheet from Ben-TechMedical, (California). Each membrane unit included a circularlyperforated metal sheet for structural support. Two of each type ofsupported membrane unit were mounted on opposite sides of a rectangularlollipop-shaped module illustrated schematically in FIG. 3. The membraneunits 31 (one shown) were placed in frames 32 to create a complete sealabout the perimeter. In the case of the composite membrane unit, thePolymer A-coated side faced outward. The housing 33, frames and membraneunits defined an interior chamber, not shown, which was supplied withgas through supply tube 34. Each membrane unit had 65 cm² surface area39 exposed through perforations 37 of metal sheet 38 to provide totalmodule effective area for gas permeation of 130 cm². When pressurized,the silicone rubber sheet membrane unit bulged hemispherically throughthe perforations of the metal sheet, effectively doubling the modulearea. After immersing a module into a 5 L reservoir of water, oxygen atthe pressure stated in Table III was fed to the supply tube. An agitatorin the reservoir was rotated driven at 50 rev. per min. during eachtrial. Oxygen was thus transferred to the water at the highest ratewithout bubbling. The dissolved oxygen concentration in water wasmeasured over a period of 30-60 minutes and the initial rate of oxygentransfer is presented in Table III.

                  TABLE III    ______________________________________                        Oxygen   O.sub.2 Transfer Rate                        pressure (mL O.sub.2 /L × 10.sup.2 /           Description  KPa (psig)                                 cm.sup.2 · min. )    ______________________________________    Ex. 17   1 μm Polymer A/100                            21 (3)   18.1             μm e-PTFE    Comp. Ex. 4             100 μm e-PTFE                            <6.89 (1)                                     8.8    Comp. Ex. 5             1250 μm Silicone Rubber                            21 (3)   5.5    ______________________________________

Data of Table III shows that a coating of 1 μm of Polymer A added toe-PTFE substrate improved oxygen delivery rate to water by over 100%.The improvement was apparently aided by the ability to pressurize thegas thereby enhancing the driving force without causing oxygen bubblesin the liquid. At higher than 6.89 KPa (1 psig) pressure, the uncoatede-PTFE membrane admitted so much oxygen that bubbles formed in thewater. At the same gas side pressure of 21 KPa (3 psig), thetransmission rate of dissolved oxygen through the novel membrane unitalso was more than three times the rate through the silicone rubbersheet. It is known that the oxygen flux through a 1 μm thickness ofPolymer A is about 4900 times that through a 1250 μm thickness ofsilicone rubber. Thus the observed delivery rate ratio of 3:1 betweenEx. 17 and Comp. Ex. 5 indicates that flux was limited by the masstransfer of oxygen in the water. Because thin coatings of PDD copolymerscan be incorporated into membrane units which pack to a surface area perunit volume density about eight times that of thick sheet membranes,this example shows that the overall gas flux improvement achievable foroxygenating water by the present invention relative to silicone rubbershould be 25-30 fold.

Example 18 and Comparative Example 6

Oxygen was transferred into water using a 1.5 L shell side, watercapacity permeator module substantially as shown in FIG. 6. The moduleemployed membrane units of hollow fibers of substrate A coated on theoutside surface with Polymer A and having effective area for gastransmission of 50 cm² (Ex. 18). Oxygen was fed on the tube side at 34.5KPa (5 psig) and water at about 26°-28° C. was passed through the shellside at 0.5 L/min. The dissolved oxygen concentration was measured eachminute up to 8 minutes. The data are identified as points "A" plotted inFIG. 4 as concentration of oxygen in water vs. time. The experiment wasrepeated at 69 KPa (10 psig) (points "B") and 138 KPa (20 psig) (points"C"). Oxygen delivery to water through a 150 μm thickness 50 cm² areamicroporous polyvinylidene fluoride ("PVDF") membrane at 34.5 KPa (5psig) (Comp. Ex. 6) was measured for comparison. The results are plottedas points "D" in FIG. 4. The figure illustrates that oxygen transmissionrate according to the novel method was equivalent to that of PVDF, ahydrophobic, microporous polymer. Additionally, it is seen that oxygentransmission rate without bubbling afforded by the novel method can bedramatically increased by increasing tube side pressure.

Examples 19-20 and Comparative Examples 7-8

High oxygen demanding, Sf-21 cells at a density of about 250×10³cells/mL were placed in Cyto-Sf-9 culture medium (Kemp Biotechnologies,Inc.) in a 5 L bioreactor at 27° C. Oxygen demand for these cells wasexperimentally measured to be about 10⁻¹⁰ mL/(min•cell). For 5-7 daysoxygen was fed to the culture medium through a 130 cm² area flat sheetmembrane unit of 1 μm thickness Polymer A coated on 100 μm thick, 0.05μm microporous expanded polytetrafluoroethylene substrate at a gas rateeffective to provide 50% of saturation. The Polymer A coated side of themembrane unit was exposed to the culture medium. The reactor was sampleddaily for cell density and viability. Viability was determined by mixinga cell population sample of selected dilution with 0.4% aqueous TrypanBlue dye and counting unstained (viable) and total cells with ahemocytometer. In all cases, viability was at least 90%. The culture wasallowed to propagate until the fail point at which the supplied oxygenwas unable to satisfy demand. Subsequently the dissolved oxygenconcentration declined to zero and the culture was terminated. The peakcell density was calculated at the fail point. In both of duplicatedeterminations, Ex. 19-20, the peak cell density was 2.7×10⁶ cells/mLindicating that 2.1×10⁴ cells/(mL•cm²) can be supported by oxygentransmitted through the novel membrane unit at test conditions.

The experiment was repeated in duplicate (Comp. Exs. 7-8) with themembrane unit replaced by 260 cm² flat sheet of 1250 μm thick siliconerubber. Fail point peak cell densities of 1.7×10⁶ cells/mL and 1.2×10⁶cells/mL were observed. These values calculate to 0.7×10⁴ and 0.5×10⁴cells/(mL•cm²) supportable cells per unit membrane area, respectively,and averaging 0.6×10⁴ cells/(ml•cm²). These examples show that themethod according to the present invention can support 3.5 times the celldensity per unit area as silicone rubber. This result is consistent withthe results of Examples 17 and Comp. Exs. 4-5.

Example 21

The novel membrane unit was shown to be non-adhesive to cells in cultureas follows. Vero cells, an established attachment dependent cell linederived from African Green Monkey kidney, was seeded into a T-75 cellculture flask containing 50/50 DMEM/F12 (10% FBS) cell culture medium. Apiece of membrane unit consisting of 1 μm layer of Polymer A coated on100 μm layer of e-PTFE was steam sterilized and placed in the flask.Cells were permitted to propagate to confluence on the glass of theflask and in contact with the membrane unit. At near-confluence, themembrane was transferred to a petri dish, washed with 1X phosphatebuffered saline (PBS) and stained with 1% Neutral Red dye. The cultureflask was similarly drained, rinsed and stained. One minute afterstaining, both the membrane and culture flask were rinsed carefully withPBS. The membrane rinsed clear of color indicating no attachment ofcells to the membrane material, however, the glass on the floor of theflasks remained red, revealing that the cells had adhered to the flask.This example demonstrates that bioreactor mass should not attach toperfluoro-2,2-dimethyl-1,3-dioxole copolymers, and therefore thematerial should provide durable service in bioreactor utility.

Example 22 and Comparative Example 9

A 130 cm² membrane unit of 1 μm thick layer of Polymer A coated on a 100μm thick layer of 0.05 μm microporous e-PTFE substrate was mounted on apermeator module substantially as shown in FIG. 3. The module was usedto oxygenate three successive Sf-21 cell cultures until each cellpopulation peaked as indicated by a drop in oxygen concentration. Eachoxygenation lasted about 5-7 days. After these oxygenations, the abilityof the membrane unit to transfer oxygen was then determined by immersingthe module in a water bath and adding oxygen. The dissolved oxygenconcentration in the bath was recorded periodically and the results areplotted in FIG. 5 as line "A". Subsequently, the membrane structure waswashed with Tergizyme™ and the water bath oxygenation measurements wererepeated. Results are plotted as line "B" in FIG. 5. These procedureswere duplicated except that a 1250 μm thick membrane of silicone rubber(Comp. Ex. 9) was used instead of the Polymer A/e-PTFE substrate. Theprewash and post wash data are plotted in FIG. 5 as lines "C" and "D",respectively.

Slopes of lines A-D indicate the oxygen transmission rate of themembrane support structures. In cleaned and fouled conditions, the novelmembrane unit oxygen transmission rates were 0.995 and 0.893mL/(L•min.), respectively, showing only a 10% oxygen transmission rateloss due to fouling. The clean and fouled oxygen transmission rates forthe silicone rubber membrane unit were 0.600 and 0.349, respectively.The silicone rubber suffered a substantial oxygen transmission rate lossof 42% which suggests that the novel membrane unit is much more suitablefor bioreactor processing than conventional material. In addition, theoxygen transmission rate of the Polymer A-coated membrane unit was muchgreater than the silicone rubber in both cleaned and fouled conditions.Even in fouled condition, the membrane unit of this invention yielded a49% higher transmission rate than the cleaned silicone rubber membrane.

Example 23 and Comparative Example 10

A permeator module of the type shown in FIG. 6 was equipped with 53 PVDFhollow fibers coated on the inside surface with a 0.5 μm thick layer ofPolymer A (Ex. 23). The PVDF hollow fibers had an inside diameter of 1mm and were 11.94 cm long, which furnished the module with 200 cm² masstransfer area. Initially deoxygenated water in a 56.8 L sealed tank wasrecirculated through the tube side of the permeator module via firstfluid inlet and outlet ports at the flow rate shown in Table IV. Air at103 KPa (15 psig) was fed to the shell side through second fluid inletport. The second fluid outlet port was capped shut. Concentration ofoxygen dissolved in the water was measured periodically using a YSImodel 55 dissolved oxygen meter. Dissolved oxygen concentration wasmeasured periodically. At two levels of dissolved oxygen, morespecifically, at 1-2 and 5-6 parts per million (ppm), the oxygentransfer rate ("OTR") was calculated from the dissolved oxygen vs. timemeasurements. The water was replaced with deoxygenated water and theprocedure was rerun without changing the permeator module. The low andhigh dissolved oxygen level OTRs were calculated as before. These OTRsare reported in Table IV.

A permeator module was prepared identically to that of Ex. 23 exceptthat the PVDF hollow fibers were not coated (Comp. Ex. 10). Twoconsecutive oxygenation runs were carried out as in Ex. 23. The resultsare shown in Table IV.

The first run OTRs at each of the high and low dissolved oxygen levelsof Ex. 23 and Comp. Ex. 10 show that the initial oxygen transmissionrate with a PDD copolymer-coated membrane unit is at least equivalent tothat of a conventional membrane unit. Comparison of the first and secondrun OTRs in each series shows that the OTR remained stable for thePDD-copolymer-coated hollow fibers. At the high dissolved oxygen level,the OTR increased in the second run. The uncoated PVDF membrane unitruns indicate that at each level of dissolved oxygen, the OTR droppedapproximately in half from the first to the second run. Thisdemonstrates an improved stability of flux according to the novelmethod.

                  TABLE IV    ______________________________________    Water    Recirculation  OTR         OTR    Flow           kg/h (lbs/h) × 10.sup.6                               kg/h (lbs/h) × 10.sup.6    (L/min.)       at 1-2 ppm  at 5-6 ppm    ______________________________________    Ex. 23    run 1  5.8         363 (800)   179 (395)    run 2  5.8         338 (745)   238 (525)    Comp. Ex. 10    run 1  7.2         254 (560)   172 (380)    run 2  7.5         166 (365)   86.2 (190)    ______________________________________

Example 24

A permeator module of the type shown in FIG. 6 was constructed from5,952 polypropylene hollow fibers of 200 μm inside diameter and 21.5 cmlength. The inside surface of each fiber was coated with a 1.0 μm thicklayer of Polymer A to provide 8,035 cm² effective mass transfer area.Water with 6.44 ppm initial dissolved oxygen concentration wasrecirculated through the air-tight tank used in Ex. 23 and the tube sideof the module at 19° C. The shell side of the module was maintainedunder vacuum of -101 KPa (30 inch Hg vacuum). Dissolved oxygenconcentration was measured periodically with a model 55 YSI dissolvedoxygen meter and the OTR was calculated therefrom. The data shown inTable V validate the ability of the PDD-copolymer coated membrane unitto degasify a liquid.

                  TABLE V    ______________________________________           Dissolved     OTR        Recirculation    Time   Oxygen Conc.  kg/h (lbs/h) ×                                    Flow Rate    min.   ppm           10.sup.6   L/min.    ______________________________________    0      6.44          --         5.0    5      6.02          286.0 (630.5)    10     5.59          292.8 (645.5)    15     5.20          265.6 (585.5)    20     4.80          272.4 (600.5)    25     4.43          251.9 (555.4)                                    4.29    30     4.27          109.0 (240.2)    35     3.98          197.4 (435.3)    40     3.82          109.0 (240.2)    45     3.59          156.6 (345.3)    50     3.46           88.5 (195.2)    60     3.1           122.6 (270.2)    70     2.8           102.2 (225.2)                                    4.0    80     2.49          105.6 (232.7)    85     2.41           54.5 (120.1)    ______________________________________

Although specific forms of the invention have been selected forillustration in the drawings and examples, and the preceding descriptionis drawn in specific terms for the purpose of describing these forms ofthe invention, this description is not intended to limit the scope ofthe invention which is defined in the claims.

What is claimed is:
 1. A method of transferring a gaseous component between two fluids having different partial pressures of the gaseous component, wherein the first of the two fluids is a liquid biological fluid, the method comprising:contacting one of the two fluids with a first side of a two-sided, membrane unit, the membrane unit including a nonporous membrane (i) being substantially impermeable to the liquid and having a permeability to oxygen of at least 100 barrers; (ii) formed from an amorphous copolymer of perfluoro-2,2-dimethyl-1,3-dioxole; and (iii) being at a temperature below the glass transition temperature of the amorphous copolymer; and simultaneously contacting the second side of the two-sided, membrane unit with the other of the two fluids.
 2. The method of claim 1 in which the liquid biological fluid is free of the gaseous component in the gaseous state.
 3. The invention of claim 1 wherein the biological fluid contains living cells.
 4. The invention of claim 3 wherein the biological fluid is blood.
 5. A method of oxygenating blood having a low blood oxygen partial pressure, the method comprising:contacting blood with a first side of a two-sided, membrane unit, the membrane unit including a nonporous membrane (i) being substantially impermeable to blood and having a permeability to oxygen of at least 100 barrers, (ii) formed from an amorphous copolymer of perfluoro-2,2-dimethyl-1,3-dioxole; and (iii) being at a temperature below the glass transition temperature of the copolymer; and simultaneously contacting the second side of the two-sided, membrane unit with a gaseous mixture containing oxygen at a partial pressure higher than the low blood oxygen partial pressure.
 6. In a bioreactor, a method of oxygenating a liquid reaction medium containing living cells and having a low oxygen partial pressure, the method comprising:contacting the liquid reaction medium with a first side of a two-sided, membrane unit, the membrane unit including a nonporous membrane (i) being substantially impermeable to the liquid reaction medium and having a permeability to oxygen of at least 100 barrers; (ii) formed from an amorphous copolymer of perfluoro-2,2-dimethyl-1,3-dioxole; and (iii) being at a temperature below the glass transition temperature of the copolymer; and simultaneously contacting the second side of the two-sided, membrane unit with a gaseous mixture containing oxygen at a partial pressure higher than the low oxygen partial pressure. 